Class 2017
PhD Grant: PD/BD/135139/2017
PhD thesis
Mechanistic insights on the role of CgHaa1- and CgPdr1- pathways in stress resilience and pathogenesis of Candida glabrata
Supervisor
• Nuno P. Mira , Professor @ IST/ULisboa, PT
Collaborators
• Frederic Devaux, Professor @ Université Pierre et Marie Curie, FR
• Paula Sampaio, Professor @ Universidade do Minho, PT
• Joana Azeredo, Professor @ Universidade do Minho, PT
Proposal summary
To successfully thrive in the genitourinary tract C. glabrata has to cope with numerous stresses including the presence of organic acids at a low pH that are produced by the co-colonizing microbiota and also azoles which are used as antifungal agents. This thesis will be focused on elucidating, at a genome-wide scale, how C. glabrata cells respond to these two stresses, either alone or in combination. Emphasis will be put on the role played by the CgPdr1 and CgHaa1 regulons, considering their demonstrated essential role in response to those stresses. It will also be examined whether these two regulatory systems may contribute for pathogenic traits of C. glabrata including virulence in different infection models or ability to form biofilms in biotic or abiotic surfaces.
Resumo de proposta de Tese
Para colonizar o trato geniturinário a C. glabrata tem que persistir a múltiplos stresses, incluindo a presença de ácidos orgânicos produzidos pela microbiota co-colonizadora num nicho de baixo pH, ou agentes antifúngicos como os azóis. Esta tese terá como objetivo elucidar, a uma escala genómica, as respostas das células de C. glabrata em específico a ambos os stresses descritos, isoladamente ou em combinação. Será dado ênfase ao papel desempenhado pelas redes transcriptomicas do CgPdr1 e CgHaa1, considerando o demonstrado essencial função destas redes na resposta a esses stresses. A contribuição de ambos os sistemas regulatórios na patogenecidade de C. glabrata, incluindo na virulência em diferentes modelos de infecção ou na capacidade de formar biofilmes em superfícies bióticas ou abióticas será também investigado.
PUBLICATIONS
Papers
Salazar, S.B., Simões, R.S., Pedro, N.A., Pinheiro, M.J., Carvalho, N.F.N.N., Mira, N.P., An overview on conventional and non-conventional therapeutic approaches for the treatment of candidiasis and underlying resistance mechanisms in clinical strains, Journal of Fungi (Basel). 10;6(1), 2020.
Salazar, S.B., Wang, C., Musterkotter, M., Okamoto, M., Takahashi-Nakagchi, A., Chibana, H., Lopes, M., Güldener, U., Butler, G. and Mira, N., “Comparative genomic and transcriptomic analyses unveil novel features of azole resistance and adaptation to the human host in Candida glabrata”, FEMS Yeast Research 1;18(1), 2018.
Oral Communications
Salazar, S.B., Valez, N., Sotti-Novais, D., Simões, R., Souza, J. A., Faustino, M. J., Faustino, C., Mendonça, C., Lopes, M. M., Vitória Rodrigues, V., Mira, N. P. “Unveiling azole resistance mechanisms in Candida glabrata clinical isolates encoding wild-type or gain-of-function CgPdr1 alleles”, Candida and Candidiasis, 21-27 March 2021, vitual event
Salazar, S.B., Pedreira, T., Chibana, H., Lopes, M.M., Güldene, U., Mira, N.P., Genomic Adaptative Mechanisms mediating Azole Resistance and Adaptation to the Human Host in Candida glabrata, with emphasis on the role of CgPDR1 regulon”, XXI Jornadas de Biologia de Leveduras, 8-9 June 2018, Braga, Portugal
Salazar, S.B., Bernardo, R., Cunha, D.V., Wang, C., Chibana, H., Silva, S., Pereira, L., Sá-Correia, I., Azeredo, J., Butler, G., Mira, N.P., “Genetic adaptive mechanisms mediating response ans tolerance to acetic acid stress in the human pathogen Candida glabrata: role of the CgHaa1-dependent signalling pathway”, Microbal Stress Meeting: Systems to Molecules and Back, 23-25 April 2018, Kinsale, Ireland (Best talk by an Early Career Researcher sponsored by the journal Genes)
Poster Communications
Salazar, S.B., Valez, N.,Pinheiro, M.J., Pedro, N.A., Lourenço, A., Mira, N. P. “Modulation of C. glabrata response and resistance to azoles in the presence of acetic and lactic acids at low pH”. Candida and Candidiasis, 21-27 March 2021, vitual event
Salazar, S., Silva, S., Mil-Homens, D., Pimenta, A.I., Chibana, H., Azeredo, J., Fialho, A.M., Mira, N.P., The Candida glabrata CgHaa1-dependent system is required for biofilm formation, adhesion to epithelial cells and maximal virulence against Galleria mellonela”, Advanced Lecture Course on Human Fungal Pathogens, 18-24 May 2019, Nice, France
Salazar, S.B., Pedreira, T., Henriques, R., Wang, C., Musterkotter, M., Okamoto, M., Takahashi-Nakaguchi, A., Chibana, H., Lopes, M.M., Güldener, U., Butler, G., Mira, N.P., “Comparative genomic and transcriptomic analysis unveil novel features of azole resistance and adaptation to the human host in Candida glabrata”, MicroBiotec2017 December 7-8, 2017, Porto, Portugal
DOCTORAL PROGRAM (36 ECTS)
Curricular units:
• General Doctoral Training (6 ECTS)
• Advanced Experimental Techniques and methodologies (6 ECTS)
• Bioentrepreneurship (6 ECTS)
• Outreach and Teaching Skills (6 ECTS)
• Advanced Topics in bioengineering and Biological Sciences (6 ECTS)
• Gene therapy (6 ECTS)
Advanced courses:
• 8th Advanced Lecture Course on Human Fungal Pathogens, by FEMS, 18-24 May 2019, La Colle sur Loup, Nice, France
• Teaching STEM Students – Transformation Guide for teaching Assistants 1st Ed., by Academic Development Office, 10-12 September 2018, Instituto Superior Técnico, Lisbon, Portugal
• Analysis of High-Throughput Sequencing Data, by European Bioinformatics Institute (EMBL-EBI), 07-10 November 2017, Welcome Genome Campus, Cambridge, UK